ABSTRACT Support is requested for a Keystone Symposia conference entitled Origins of Allergic Disease: Microbial, Epithelial and Immune Interactions, organized by Drs. Marsha Wills-Karp, Donald Leung and Kari Nadeau. The conference will be held in Granlibakken Tahoe, Tahoe City, California from March 24-27, 2019. Allergic diseases have been on the rise globally in recent decades. Although it has long been known that IgE- mediated immune responses are associated with the manifestations of a wide spectrum of allergic disorders (asthma, atopic dermatitis, atopic rhinitis, food allergy, eosinophilic esophagitis), the exact factors leading to these aberrant immune responses are not well understood. Recent insights into disease origins support a broader realm of factors that may predispose, initiate or exacerbate altered immunity in allergic diseases such as inherent epithelial barrier dysfunction, loss of immune tolerance at central and specific sites, disturbances in gut and organ specific microbiomes, diet, and age. However, these studies are in their infancy and have only been considered in a reductionist, disease or tissue specific manner to date. Few studies have addressed the cross-talk between various organs leading to the concept of allergy as a System Disease. A better understanding of the distinct or shared complex web of factors underlying the spectrum of allergic disorders and the successes/failures of the current armature of therapies may lead to the development of safer, disease-modifying interventions in the future. Thus the major goal of this meeting is to explore the potential microbial-epithelial- immune interactions underlying the etiology of allergic disorders in order to promote the development of novel disease prevention or intervention strategies.